Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30)
Marek's disease is a natural model for lymphomas overexpressing Hodgkin's disease antigen (CD30)
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DOI：
10.1073/pnas.0305789101
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发表时间：
2004-09-21
影响因子：
11.1
通讯作者：
Davison, TF
中科院分区：
文献类型：
--
作者：
Burgess, SC;Young, JR;Davison, TF
动物模型对于阐明癌变的分子机制至关重要。霍奇金淋巴瘤和许多不同的非霍奇金淋巴瘤过表达霍奇金病抗原CD30(CD30(hi))，一种肿瘤坏死因子受体II家族成员。本研究表明，鸡马立克氏病（MD）淋巴瘤细胞也是CD30(hi)，是CD30hi淋巴瘤的独特天然模型。鸡的CD30类似于一种祖先形式，我们在鸡、人类和小鼠的CD30中发现了一个先前描述过的潜在细胞质信号域。我们的系统发育分析定义了人类和小鼠CD30结构之间的关系，并证实小鼠CD30代表了祖先哺乳动物的基因结构。MDV转化淋巴细胞的CD30表达与MDV Meq推定致癌基因（c-Jun同源物）在体内的表达相关。鸡CD30启动子具有15个预测的高强度Meq结合转录因子识别基序，并且Meq在体外增强CD30启动子的转录。血浆蛋白质组学鉴定出CD30的可溶性形式。CD30过表达在进化上是保守的，并定义了一类肿瘤转化事件，无论病因如何。我们提出CD30是肿瘤转化过程中受到干扰的关键细胞内信号通路的一个组成部分。致癌性MDV感染基因md抗性鸡后出现特异性抗CD30 igg，提示对CD30的免疫可能在MID淋巴瘤消退中发挥作用。
Animal models are essential for elucidating the molecular mechanisms of carcinogenesis. Hodgkin's and many diverse non-Hodgkin's lymphomas overexpress the Hodgkin's disease antigen CD30 (CD30(hi)), a tumor necrosis factor receptor II family member. Here we show that chicken Marek's disease (MD) lymphoma cells are also CD30(hi) and are a unique natural model for CD30hi lymphoma. Chicken CD30 resembles an ancestral form, and we identify a previously undescribed potential cytoplasmic signaling domain conserved in chicken, human, and mouse CD30. Our phylogeneic analysis defines a relationship between the structures of human and mouse CD30 and confirms that mouse CD30 represents the ancestral mammalian gene structure. CD30 expression by MD virus (MDV)-transformed lymphocytes correlates with expression of the MDV Meq putative oncogene (a c-Jun homologue) in vivo. The chicken CD30 promoter has 15 predicted high-stringency Meq-binding transcription factor recognition motifs, and Meq enhances transcription from the CD30 promoter in vitro. Plasma proteomics identified a soluble form of CD30. CD30 overexpression is evolutionarily conserved and defines one class of neoplastic transformation events, regardless of etiology. We propose that CD30 is a component of a critical intracellular signaling pathway perturbed in neoplastic transformation. Specific anti-CD30 Igs occurred after infection of genetically MD-resistant chickens with oncogenic MDV, suggesting immunity to CD30 could play a role in MID lymphoma regression.